期刊
THERANOSTICS
卷 7, 期 16, 页码 3876-3888出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.19547
关键词
Angiogenesis; PET-CT; Dimeric-cRGD; Multimodal imaging; Peripheral arterial disease (PAD); Diabetes; Muscle-derived mesenchymal stem cells (mMSCs)
资金
- AHA Scientist Development Grant [10SDG4180043]
- Arnold Beckman Foundation
- Diabetes Complications Consortium DiaComp [25732-27]
- National Science Foundation Integrative Graduate Education and Research Traineeship (IGERT) in Cellular and Molecular Mechanics and BioNanotechnology
- National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health [T32EB019944]
Peripheral arterial disease (PAD) is a debilitating complication of diabetes mellitus (DM) that leads to thousands of injuries, amputations, and deaths each year. The use of mesenchymal stem cells (MSCs) as a regenerative therapy holds the promise of regrowing injured vasculature, helping DM patients live healthier and longer lives. We report the use of muscle-derived MSCs to treat surgically-induced hindlimb ischemia in a mouse model of type 1 diabetes (DM-1). We serially evaluate several facets of the recovery process, including alpha(V)beta(3)-integrin expression (a marker of angiogenesis), blood perfusion, and muscle function. We also perform microarray transcriptomics experiments to characterize the gene expression states of the MSC-treated is-chemic tissues, and compare the results with those of non-ischemic tissues, as well as ischemic tissues from a saline-treated control group. The results show a multifaceted impact of mMSCs on hindlimb ischemia. We determined that the angiogenic activity one week after mMSC treatment was enhanced by approximately 80% relative to the saline group, which resulted in relative increases in blood perfusion and muscle strength of approximately 42% and 1.7-fold, respectively. At the transcriptomics level, we found that several classes of genes were affected by mMSC treatment. The mMSCs appeared to enhance both pro-angiogenic and metabolic genes, while suppressing anti-angiogenic genes and certain genes involved in the inflammatory response. All told, mMSC treatment appears to exert far-reaching effects on the microenvironment of ischemic tissue, enabling faster and more complete recovery from vascular occlusion.
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